{"ID": "PMID:30799036", "aka": "https://www.biorxiv.org/content/early/2017/08/03/171801", "lab": {"uuid": "cf795e33-7877-47e8-9534-4369487976b6", "display_title": "Tom Misteli, NCI", "correspondence": [{"contact_email": "bWlzdGVsaXRAbWFpbC5uaWguZ292", "@id": "/users/30d53a1e-4468-400d-924d-ba797c03d580/", "display_title": "Tom Misteli"}], "title": "Tom Misteli, NCI", "@id": "/labs/tom-misteli-lab/", "status": "current", "@type": ["Lab", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "submits_for.cf795e33-7877-47e8-9534-4369487976b6"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/30799036", "award": {"@id": "/awards/1U54DK107980-01/", "@type": ["Award", "Item"], "project": "4DN", "description": "NOFIC: The spatial organization of the genome impinges on all genomic processes, including gene regulation, maintenance of genome stability and chromosome transmission to daughter cells. A detailed understanding of the spatial arrangement of the human genome, referred to as the 4D nucleome, and the biological and physical principles that drive chromosome folding requires combining approaches from the fields of molecular and cell biology, imaging, genetics and genomics with approaches from physics, computational biology, and computer simulation. We have assembled a highly interdisciplinary center with the goal of generating extensively validated maps of the 4D nucleome, its physical and dynamic properties and its role in regulating the activity of the genome. First, the center will further optimize and extensively validate a suite of genome-wide molecular methodologies, based on chromosome conformation capture (3C) that can probe the folding of chromosomes at the scale of single nucleosomes, chromatin fibers, chromosomes and the entire nucleus, across cell populations and in single cells. Given that chromosome and nuclear organization is tightly linked to biological state of the cell, the center will map the 4D nucleome for four key biological states representing different conformations during the cell cycle (interphase and mitosis), and during cell differentiation (pluripotent and differentiated states). We will obtain complementary data regarding the structure and dynamics of chromatin, at different length scales and in single cells using extensive high-throughput imaging, live cell imaging and super resolution microscopy. Data obtained with all approaches will be analyzed, integrated and modeled using a set of methods we will further develop to gain insights into the structure, physics and dynamics of chromosome folding over different length scales. Finally, a critical component of our proposal is the biological validation and further elaboration of the chromatin interaction maps that are generated from our conformational analyses. This validation will be achieved through site-specific editing of genomic sequence and epigenetic marks, the creation of new contact points within the genome, and the identification of factors (both protein and nucleic acid) that facilitat or restrict these interactions. Effects of such perturbations in the chromosome conformation on transcription will reveal relationships between specific chromosome structural features and gene expression.", "uuid": "ae6c618f-7a8c-441e-a886-e30bbbe591da", "status": "current", "display_title": "CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME", "center_title": "NOFIC - Dekker", "name": "1U54DK107980-01", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization.", "status": "current", "aliases": ["dcic:misteli_finn_2017"], "authors": ["Finn EH", "Pegoraro G", "Brandao HB", "Valton AL", "Oomen ME", "Dekker J", "Mirny L", "Misteli T"], "journal": "Cell", "abstract": "Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population.", "date_created": "2017-10-11T21:36:21.312793+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2019-02-27T16:23:29.729797+00:00"}, "date_published": "2019-02-01", "public_release": "2018-02-26", "schema_version": "2", "static_content": [{"content": {"@id": "/static-sections/35799cfd-dcfa-47fc-a845-8e2de84c89ba/", "award": {"status": "current", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "name": "finn_et_al_summary", "content": "

Finn et al systematically probed the heterogeneity in genome organization in human fibroblasts by combining high-resolution Hi-C datasets and high-throughput genome imaging. High-throughput Imaging Position MAPing (HIPMap) based on high-throughput fluorescence in situ hybridization (hiFISH) was used to systematically determine the spatial position and distances between combinations of genomic interaction pairs identified by Hi-C.

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Dilution Hi-C experiments were performed with HFF-hTERT cells, and various loci were chosen on chromosomes 1, 17 and 18 to test distances of different pairs of loci with high-throughput DNA-FISH (HIPMap). Interaction of TADs was also probed on chromosome 4. Here you can find a summary of the experiments performed.

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Microcopy Dataset

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Aim

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Target List

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DNA-FISH on Chr1

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Testing different Hi-C frequencies

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Genomic regions on Chr1

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DNA-FISH on Chr17

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Testing different Hi-C frequencies

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Genomic regions on Chr17

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DNA-FISH on Chr18

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Testing different Hi-C frequencies

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Genomic regions on Chr18

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DNA-FISH on Chr1 and 17

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Testing different Hi-C frequencies

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-

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DNA-FISH on Chr4

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Testing TAD interaction

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Genomic regions on Chr4

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Figure produced on 4DN Jupyter Hub, with notebook examples/Finn et al, Microscopy and HiC data overlaid

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